The DOI matches its Crossref record; 52 of the 53 references it cites were found in a registry or an index.
The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line
Open accessAbstract
Since 1987, immortalized cells from the ovary of a Chinese hamster have been the workhorse for producing recombinant therapeutics, including monoclonal antibodies, blood factors, hormones, growth factors and enzymes. Xu et al. provide the genome sequence of the ancestral CHO-K1 cell line, which should aid in the optimization of current production cell lines. Chinese hamster ovary (CHO)–derived cell lines are the preferred host cells for the production of therapeutic proteins. Here we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45 Gb of genomic sequence, with 24,383 predicted genes. We associate most of the assembled scaffolds with 21 chromosomes isolated by microfluidics to identify chromosomal locations of genes. Furthermore, we investigate genes involved in glycosylation, which affect therapeutic protein quality, and viral susceptibility genes, which are relevant to cell engineering and regulatory concerns. Homologs of most human glycosylation-associated genes are present in the CHO-K1 genome, although 141 of these homologs are not expressed under exponential growth conditions. Many important viral entry genes are also present in the genome but not expressed, which may explain the unusual viral resistance property of CHO cell lines. We discuss how the availability of this genome sequence may facilitate genome-scale science for the optimization of biopharmaceutical protein production.
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“The availability of genomic sequences has enabled CHO cell engineering with unprecedented precision using engineered nucleases, including zinc finger nucleases (ZFNs) and transcription activator like nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR) system [71–73,75,76].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [71]
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“CHO cells do not express alpha-1,3-galactosyltransferases, which produce the immunogenic alpha-galactosyl epitope (although they have the gene), and the expression of CMP-N-acetylneuraminic acid hydroxylase, which produces CMP-NeuGc, is virtually absent [27,71,72].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [71]
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“Advances in various omics technologies have significantly improved our understanding of CHO cells at different levels and enabled the rational targeting of glycosylation effectors for improved biopharmaceutical production [27,71,72,150–152].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [71]
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Cites
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“This is consistent with the observation that CHO cells do not normally show ST6Gal activity19, whereas terminal α(2,3)-linked sialic acid residues are abundant.”
InfluentialAssembly algorithms for next-generation sequencing data
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“For some of these proteins, differential glycosylation can substantially affect functional activity and/or in vivo circulatory half-lif”
Annotation, submission and screening of repetitive elements in Repbase: RepbaseSubmitter and Censor
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Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma
Sung, W.-K. K., Zheng, H., Li, S., Chen, R., Liu, X., Li, Y., Lee, N. P. Y., Lee, W. H., Ariyaratne, P. N., Tennakoon, C., et al. (2012) · Nature Genetics · doi:10.1038/ng.2295 · Cited by 985
Self-citationBennett, E. P., Mandel, U., Clausen, H., Gerken, T. A., Fritz, T. A., & Tabak, L. A. (2012) · Glycobiology · doi:10.1093/glycob/cwr182 · Cited by 876
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Self-citationKim, J. Y., Kim, Y.-G., & Lee, G. M. (2012) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-011-3758-5 · Cited by 801
Human cell lines for biopharmaceutical manufacturing: history, status, and future perspectives
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Metadata
- Authors
- Xu, X., Nagarajan, H., Lewis, N. E., Pan, S., Cai, Z., Liu, X., Chen, W., Xie, M., Wang, W., Hammond, S., Andersen, M. R., Neff, N., Passarelli, B., Koh, W., Fan, H. C., Wang, J., Gui, Y., Lee, K. H., Betenbaugh, M. J., Quake, S. R., Famili, I., Palsson, B. O., & Wang, J.
- Affiliations
- BGI Group (China) (CN)
- Peking University Shenzhen Hospital (CN)
- Delaware Biotechnology Institute (US)
- Technical University of Denmark (DK)
- Howard Hughes Medical Institute (US)
- Johns Hopkins University (US)
- Corresponding author
- Wang, Jianbin
- Wang, Jun
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2011-08
- Volume
- 29
- Issue
- 8
- Pages
- 735-741
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC3164356
- OpenAlex
- W2093343938
- Cited by
- 785
- References
- 53
- Citations by year
- 2026: 22 · 2025: 25 · 2024: 37 · 2023: 35 · 2022: 39 · 2021: 58 · 2020: 38 · 2019: 45 · 2018: 78 · 2017: 57 · 2016: 59 · 2015: 77 · 2014: 79 · 2013: 64 · 2012: 53
- FWCI
- 27.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Biotechnology (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
- Funders
- Novo Nordisk Fonden (NNF10CC1016517)
- National Cancer Institute (R44CA139977)
- National Center for Research Resources (P20RR016472)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Keywords
- CHO-K1 cells, CHO cells, draft genome sequence, therapeutic protein production, monoclonal antibodies, virus resistance, cell line engineering, genome assembly, gene expression
- MeSH terms
- Animals, Chromosome Mapping, Cricetulus, Glycosylation, Cricetinae, Models, Biological, Molecular Sequence Data, CHO Cells, Genome, Sequence Analysis, DNA, Genomics
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